The hypotriglyceridemic action of omega-3 (n-3) fatty acids is attributed primarily to reduction in hepatic triglyceride synthesis and reduced secretion of very-low-density lipoproteins (VLDLs). However, increased catabolism of triglyceride-rich lipoproteins was reported and could be due to increased availability of peripheral lipoprotein lipase (LPL) or hepatic lipase (HL). In this study plasma lipoproteins and postheparin activities of LPL and HL were determined in 12 patients with primary hypertriglyceridemia before and during isocaloric substitution of omega-3 fatty acids (10 g/d) for 4 wk. Omega-3 polyunsaturates resulted in 53% and 61% reductions in plasma triglyceride and VLDL-cholesterol concentrations, respectively (P less than 0.0001). However, low-density-lipoprotein (LDL)-cholesterol concentrations increased by 26% (P less than 0.001). Activities of postheparin LPL and HL essentially remained the same. Thus, in patients with primary hypertriglyceridemia, reduction in plasma triglyceride concentrations and increase in LDL-cholesterol concentrations mediated by omega-3 polyunsaturates seem to occur without an increase in LPL or HL activities.